Previous chapters have discussed the category of inferential statistics called parametric procedures cardura 4 mg otc arteria obstruida 50. Nonparametric procedures are still inferential statistics for deciding whether the differ- ences between samples accurately represent differences in the populations generic 1 mg cardura with amex arrhythmia jet, so the logic here is the same as in past procedures. In this chapter, we will discuss (1) two common procedures used with nominal scores called the one-way and two-way chi square and (2) review several less common procedures used with ordinal scores. Previous parametric procedures have required that dependent scores reflect an interval or ratio scale, that the scores are normally distributed, and that the population variances are homogeneous. It is better to design a study that allows you to use parametric proce- dures because they are more powerful than nonparametric procedures. However, some- times researchers don’t obtain data that fit parametric procedures. Some dependent variables are nominal variables (for example, whether someone is male or female). Sometimes we can measure a dependent variable only by assigning ordinal scores (for example, judging this participant as showing the most of the variable, this one second- most, and so on). But if the data severely violate the rules, then the result is to increase the probability of a Type I error so that it is much larger than the alpha level we think we have. Therefore, when data do not fit a parametric procedure, we turn to nonparametric statistics. They do not assume a normal distribution or homogeneous variance, and the scores may be nominal or ordinal. By using these procedures, we keep the probability of a Type I error equal to the alpha level that we’ve selected. Therefore, it is important to know about nonparametric procedures because you may use them in your own research, and you will definitely encounter them when reading the research of others. With nominal variables, we do not measure an amount, but rather we categorize participants. Thus, we have nominal variables when counting how many individuals answer yes, no, or maybe to a question; how many claim to vote Republican, Democra- tic, or Socialist; how many say that they were or were not abused as children; and so on. In each case, we count the number, or frequency, of participants in each category. For example, we might find that out of 100 people, 40 say yes to a question and 60 say no. These numbers indicate how the frequencies are distributed across the categories of yes/no. As usual, we want to draw inferences about the population: Can we infer that if we asked the entire popu- lation this question, 40% would say yes and 60% would say no? To make inferences about the frequencies in the population, we perform chi square (pronounced “kigh square”). The chi square procedure is the nonparametric inferential procedure for testing whether the frequen- cies in each category in sample data represent specified frequencies in the population. Theoretically, there is no limit to the number of categories—levels—you may have in a variable and no limit to the number of variables you may have. Here we examine the relationship between the different categories and the frequency with which participants One-Way Chi Square 353 fall into each. We ask, “As the categories change, do the frequencies in the categories also change? Being right-handed or left-handed is related to brain organiza- tion, and many of history’s great geniuses were left-handed. Then we ask them whether they are left- or right-handed (ambidextrous is not an option). The total numbers of left- and right- handers are the frequencies in the two categories. The results are shown here: Handedness Left-Handers Right-Handers fo 10 fo 40 k 2 N total fo 50 Each column contains the frequency in that category. The sum of the fos from all categories equals N, the total number of participants. Above, 10 of the 50 geniuses (20%) are left-handers, and 40 of them (80%) are right- handers. Therefore, we might argue that the same distribution of 20% left-handers and 80% right-handers would occur in the population of geniuses. Maybe, by luck, the people in our sample are unrepresenta- tive, so in the population of geniuses, we would not find this distribution of right- and left-handers.

Other drug classes used include a-adrenergic receptor agonists such as epinephrine and diuretics such as acetazolamide buy cardura 4 mg online blood pressure chart diastolic high. Carbachol is rarely used except if pilocarpine is ineffective as a treatment for open-angle glaucoma cardura 1 mg overnight delivery arrhythmia beta blocker. Varenicline (Chantix), a direct-acting nicotinic receptor agonist, is approved for use in smoking cessation (Chapter 5 X D 2). The adverse effects associated with direct-acting muscarinic cholinoceptor agonists are extensions of their pharmacologic activity. The most serious include nausea, vomiting, sweating, salivation, bronchoconstriction, decreased blood pressure, and diarrhea, all of which can be blocked or reversed by atropine. These drugs are contraindicated in the presence of peptic ulcer (because they increase acid secretion), asthma, cardiac disease, and Parkinson disease. Neostigmine and physostigmine are examples of carbamic acid esters of alcohols (carba- mates) with either quaternary or tertiary ammonium groups. Echothiophate and isoflurophate are examples of organic derivatives of phosphoric acid. Hydrolysis of the carbamylserine residue is much slower than that of acetylserine (30 min–6 h). It binds the anionic site and undergoes a nucleophilic reaction with P¼O group of alkylphosphorylated serine to cause hydrolysis of the phosphoserine bond that is at 6 least 10 times faster than that occurring in water. With the major exception of arteriole tone and blood pressure, where their effects are less pronounced, the pharmacologic effects of indirect-acting parasympathomimetic agents are similar to those of direct-acting muscarinic cholinoceptor agonists. The effect is more pronounced if muscle contraction is already weak, as occurs in myasthenia gravis. Glaucoma (1) Physostigmine is often used concurrently with pilocarpine for maximum effect in the treatment of acute angle-closure glaucoma, a medical emergency. Myasthenia gravis (1) Myasthenia gravis is an autoimmune disease in which antibodies complex with nico- tinic receptors at the neuromuscular junction to cause skeletal muscle weakness and fa- tigue. Neostigmine or edrophonium can be used following surgery to reverse neuromuscular blockade and paralysis resulting from adjunct use of nondepolarizing agents. Atropine and scopolamine poisoning can be treated with physostigmine, which reverses the central and (to some extent) the peripheral effects of competitive muscarinic antagonists. The adverse effects associated with indirect-acting sympathomimetic agents are an exten- sion of pharmacologic activity and arise from excessive cholinergic stimulation. Adverse effects include muscarinic effects similar to those of direct-acting cholinergic drugs and nicotinic effects such as muscle weakness, cramps and fasciculations, exces- sive bronchial secretions, convulsions, coma, cardiovascular collapse, and respiratory failure. Treatment includes the following steps: (1) Maintain respiration and decontaminate to prevent further absorption. Muscarinic-receptor antagonists produce cycloplegia by blocking parasympathetic tone, leading to paralysis of the ciliary muscle and loss of accommodation. These drugs produce mydriasis by blocking parasympathetic tone to the iris circular (con- strictor) muscle. Unopposed sympathetic stimulation of the radial muscle results in dilation of the pupil. These drugs dilate blood vessels in facial blush area (atropine flush), which is not related to the antagonist action. These drugs reduce peristalsis, resulting in prolonged gastric emptying and intestinal transit. Muscarinic-receptor antagonists produce some bronchodilation and decrease mucus secretion. These drugs relax the ureters and bladder in the urinary tract and constrict the urinary sphincter. Tertiary amines can produce restlessness, headache, excitement, hallucinations, and delirium. These drugs produce anhidrosis and dry skin because of the inhibition of sympathetic cho- linergic innervation of the sweat glands. Longer-acting muscarinic-receptor antagonists (such as homatropine) are generally pre- ferred as adjuncts to phenylephrine to prevent synechia formation in anterior uveitis and iritis. Cardiovascular system uses are limited and include the administration of these drugs as a treatment for acute myocardial infarction with accompanying bradycardia and hypotension or arrhythmias (e.

General anesthesia is characterized by a loss of consciousness order cardura 4 mg with amex arrhythmia update 2015, analgesia cardura 2mg sale blood pressure juicing, amnesia, skeletal muscle relaxation, and inhibition of autonomic and sensory reflexes. Balanced anesthesia refers to a combination of drugs used to take advantage of individual drug properties while attempting to minimize their adverse actions. The stages and planes of anesthesia identify the progression of physical signs that indicate the depth of anesthesia. Newer, more potent agents progress through these stages rapidly, and therefore, the stages are often obscured. Mechanical ventila- tion and the use of adjunct drugs also obscure the signs indicating the depth of anesthesia. Nitrous oxide, isoflurane, desflurane, and sevoflurane are the most commonly used inhala- tion anesthetics. They decrease cerebral vascular resist- ance with increased perfusion of the brain. These anesthetics are all respiratory depressants; consequently, assisted or controlled venti- lation is usually necessary during surgical anesthesia. Also, they are generally administered with nitrous oxide, which decreases the extent of cardiovascular and respiratory depression at equivalent anesthetic depths. Inhalation and intravenous anesthetic agent interaction with discrete protein binding sites in nerve endings to activate ligand-gated ion channels best explains their mechanism of action. Ligand-gated potassium (K ) channels, where these anesthetic agents increase potassium conductance to hyperpolarize and inhibit neuronal membrane activity 3. The relative solubility of an inhalation anesthetic in blood relative to air is defined by its blood–gas partition coefficient, lambda (k), which is directly related to the pharmacoki- netics of an anesthetic (see Table 5-9): λ =[anesthetic] in blood/[anesthetic] in gas Relatively few molecules of an anesthetic with low solubility in blood are necessary to increase its partial pressure in blood. Increased pulmonary flow from, for example, increased cardiac output decreases the rate of rise in partial pressure by presenting a larger volume of blood into which the anesthetic can dissolve. Conversely, decreased pulmonary flow, such as occurs during shock, increases the rate of induction of anesthesia. For soluble anesthetics, the longer the exposure, the lon- ger the time to recovery, because of accumulation of anesthetic in various tissues. Other factors that affect recovery include pulmonary ventilation and pulmonary blood flow. Nitrous oxide (N2O) (1) Advantages (a) Nitrous oxide is an anesthetic gas that has good analgesic and sedative properties but no skeletal muscle relaxant properties. When given in large volumes, it increases the volume of uptake of a second blood-soluble gas such as halothane (second-gas effect), which then speeds the induction of anesthesia. Isoflurane (1) Advantages (a) Isoflurane produces more rapid induction and emergence than halothane. However, paradoxically, isoflur- ane may precipitate cardiac ischemia in patients with underlying coronary heart disease. Desflurane (1) Advantages (a) Desflurane produces more rapid induction and rapid emergence than isoflurane and, therefore, is often preferred for outpatient surgical procedures. Sevoflurane (1) Advantages (a) Sevoflurane produces a very rapid and smooth induction and rapid recovery with no respiratory irritation. Sevoflurane produces fluoride ions during its liver metabolism that potentially could be nephrotoxic. Halothane (1) Advantages (a) Halothane has a pleasant odor and produces a smooth and relatively rapid induc- tion. Enflurane (1) Advantages (a) Enflurane produces a rapid induction and recovery with little excitation. It is less likely than halothane to sensitize the heart to catecholamines or cause arrhythmias. Inhalation anesthetics are bronchodilators, particularly halothane and sevoflurane, which allows use in patients with underlying respiratory problems. It is highly metabolized, resulting in dose- related fluoride-induced renal toxicity. Inhalation anesthetics, except nitrous oxide, relax uterine muscle, an advantage during cer- tain obstetrical procedures. Inhalation anesthetics increase cerebral blood flow, which may indirectly result in increased intracranial pressure.

Some of the limitations to be considered are: • Such studies are costly and can be justiﬁed only if there is a reproducible association between genotype and a clinically relevant phenotype buy 4mg cardura free shipping arrhythmia junctional. It may reﬂect real population differences but multiple comparisons cardura 2 mg free shipping arteria maxilar, biases and other design limitations suggest that many initial positive associations represent Type I errors. In selected situations, pharmacogenomic studies in healthy volunteers may sup- port a decision to perform such prospective association studies. If the results of these studies are signiﬁcant and potential health or economic beneﬁts of therapy are considerable, a major clinical trial can be considered to assess the usefulness of a pharmacogenomics-based therapy. Universal Free E-Book Store Current Status and Future Prospects of Pharmacogenomics 157 An alternative to prospective controlled clinical trials is simple examination of a treated population in a clinic by retrospective genotyping. This would reveal indi- viduals that had received treatment by chance from those where it would have been recommended on basis of genotype as well as individuals that received inappropri- ate treatment. This approach could produce valuable data to support the value of pharmacogenomic testing. The authors of this proof-of-concept study propose a shift in the current paradigm to consider the gene as the genomic feature of interest in pharmacoge- nomics discovery. Even, the full potential of currently available data about pharmacogenomics is largely unrealized because of the logistic challenges in obtaining suitable genomic information in a timely manner to guide prescribing. Placing genomic information in the electronic medical record would facilitate personalized medicine. Although this scenario holds great promise, the utility of genomic information for drug prescribing must be documented with rigorous evidence. There are many challenges ahead before personalized medicine can be truly embedded in health care (Collins and Hamburg 2013). There is a need to continue to uncover variants within the genome that can be used to predict disease onset, affect progression, and modulate drug response. New genomic ﬁndings need to be validated before they can be integrated into medical decision making. Doctors and other health care profes- sionals will need support in interpreting genomic data and their meaning for indi- vidual patients. Patients will want to be able to talk about their genetic information Universal Free E-Book Store 158 5 Pharmacogenomics with their doctor. With the right information and support, patients will be able to participate alongside their doctors in making more informed decisions. Even the most promising technologies cannot fully realize their potential if the relevant pol- icy, legal, and regulatory issues are not adequately addressed. A review of the literature indicates that pharmacogenomic research has focused mainly on non-communicable disease such as cancer, cardiovascular diseases, and neurologi- cal disorders but paid little attention to infections and orphan diseases (Olivier and Williams-Jones 2014). Analytical strategies for discovery and replication of genetic effects in pharmacogenomic studies. Now that the human genome has been sequenced, we face the greater challenge of making use of this information for improving healthcare and discovering new drugs. A detailed discussion of proteomics is given in a special report on this topic (Jain 2015). Application to development of personal- ized medicine will be discussed here brieﬂy. Role of proteomics in drug discovery and development is termed “pharmacopro- teomics” and is a more functional representation of patient-to-patient variation than that provided by genotyping, which indicates its important role in the development of personalized medicine (Jain 2004). Pharmacoproteomics is parallel to pharma- cogenomics and is used for subtyping patients on the basis of protein analysis. Proteomics-based characterization of multifactorial diseases may help to match a particular target-based therapy to a particular biomarker in a subgroup of patients. By classifying patients as responders and non-responders, this approach may accel- erate the drug development process. Because it includes the effects of post- translational modiﬁcation, pharmacoproteomics connects the genotype with the phenotype – a connection that is not always predicted by genotyping alone. Proteomics-based characterization of multifactorial diseases may help to match a particular target-based therapy to a particular marker in a subgroup of patients. Individualized therapy may be based on differential protein expression rather than a genetic polymorphism.